Cadmium (Cd) is an environmental pollutant which triggers toxic effects on various tissues, including the kidney. Proximal tubular cell damage is characteristic of Cd-induced renal toxicity. In our previous study, DNA microarray results showed that Cd treatment changed the expression levels of many genes in HK-2 human proximal tubular cells. Among the genes which increased their expression levels after Cd treatment, there were several genes coding for heat shock proteins. In the current study, we examined the role of heat shock protein genes in Cd-induced toxicity in HK-2 cells. Cd treatment increased the expression of the HSPA1, HSPH1, and HSPA8 genes in HK-2 cells. From these identified genes, only knockdown of HSPH1 and HSPA8 by siRNA treatment was found to decrease the viability of low-dose Cd-treated HK-2 cells compared with the control siRNA treatment group. These results suggest that several heat shock proteins are involved in the pathway which protects HK-2 cells against Cd toxicity.